D-1-like dopamine receptor activation and natriuresis by nitrocatechol COMT inhibitors

• Type: Article in International Scientific Journal
• Date: 2001

Authors

vieira-coelho, ma (Author) FMUP; gomes, p (Author) Other; serrao, mp (Author) Other; soares-da-silva, p (Author) FMUP

Journal

Title: Kidney International

Vol. 59

Pages: 1683-1694

ISSN: 0085-2538

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 27 Citations

Scopus - 25 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-000-VQ8

DOI: 10.1046/j.1523-1755.2001.0590051683.x

Abstract (EN): Background. In recent years, several nitmcatechol derivatives (tolcapone, entacapone, and nitecapone) have been developed and found to be highly selective and potent inhibitors of catechol-O-methyltransferase (COMT). More recently, natriuretic properties were described for two of these compounds (entacapone and nitecapone), although this was not accompanied by enhanced urinary excretion of dopamine. We hypothesized that nitrocatechol derivatives stimulate D-1-like dopamine receptors. Methods. Adult male Wistar rats were treated with a nitrocatechol COMT inhibitor (entacapone, tolcapone, or nitecapone, 39 mg/kg, orally), and the urinary excretion of dopamine and sodium was quantitated. The interaction of nitrocatechol derivatives with D-1-like receptors was evaluated by their ability to displace [H-3]-Sch23390 binding from membranes of rat renal cortex and cAMP production in opossum kidney (OK) cells. Results. Urinary excretion of sodium (mu mol/h) was markedly increased by all three nitrocatechol derivatives: vehicle, 55.0 +/- 5.6; entacapone, 98.4 +/- 9.3; tolcapone, 97.5 +/- 9.3; and nitecapone, 120.5 +/- 12.6. Pretreatment with the selective, antagonist Sch 23390 (60 mug/kg) tsmpletely prevented their natriuretic effects. Nitecapcane and tolcapone were equipotent (IC50, of 48 and 42 mu mol/L) and more potent than entacapone and dopamine (IC(50)s, of 107 and 279 mu mol/L) in displacing [H-3]-Sch23390 binding. In OK cells, all three nitrocatechol derivatives significantly increased cAMP accumulation and reduced Na+/H+ exchange and Na+,K+-ATPase activities, this being prevented by a blockade of D-1-like receptors. Conclusion. Stimulation of D-1-like dopamine receptors and inhibition of Na+/H+ exchange and Na+,K+-ATPase activities by nitrocatechol COMT inhibitors may contribute to natriuresis produced by these compountls.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12